What is Glucocorticoid Withdrawal Syndrome: 5 Things All Patients with Cortisol (Cushing) Issues Need to Know

If you’ve been diagnosed with Cushing syndrome or any condition involving excess cortisol, you’re likely preparing for or recovering from surgery to address the root cause. While surgery can be a life-changing step toward remission, the journey doesn’t end there. One challenge that many patients face post-surgery is Glucocorticoid Withdrawal Syndrome (GWS), a condition that can make recovery feel like a rollercoaster. At the Carling Adrenal Center, we’re committed to helping patients navigate this complex phase with expert care and clear guidance. Based on important research from the European Journal of Endocrinology (Zhang et al., 2023), here are five key things every patient with cortisol issues needs to know about GWS.

What is Glucocorticoid Withdrawal Syndrome (GWS)?

GWS is a cluster of symptoms that can occur after surgery for Cushing syndrome, when the body’s cortisol levels drop significantly following the removal of a cortisol-producing tumor (from the pituitary, adrenal glands, or ectopic sources). Cushing syndrome, whether caused by an adrenal tumor, pituitary tumor, or ectopic ACTH-producing lesion, leads to prolonged exposure to high cortisol levels, which suppresses the body’s natural cortisol production via the hypothalamic-pituitary-adrenal (HPA) axis. After successful surgery, this suppression can result in adrenal insufficiency, requiring glucocorticoid (steroid) replacement therapy. However, at the Carling Adrenal Center, when possible, we perform a partial adrenalectomy, which has proven to reduce the dose and duration of glucocorticoid replacement and thus decreases symptoms caused by GWS.

However, even with steroid replacement, many patients experience GWS, which mimics adrenal insufficiency symptoms but is distinct. It’s triggered by the body’s adjustment to lower cortisol levels after being accustomed to excess. According to the study by Zhang et al., GWS affects a significant number of patients—86% reported at least one symptom in the first 12 weeks post-surgery. Understanding GWS is critical because it can catch patients off guard, making them feel unwell despite being surgically cured.

What Symptoms Should You Look For?

The symptoms of GWS can be frustratingly vague and overlap with those of adrenal insufficiency, which makes it tricky to identify without proper medical guidance. The Zhang et al. study tracked patients over 12 weeks post-surgery and found that the most common GWS symptoms include:

• Myalgias and arthralgias (muscle and joint pain): Reported by 50% of patients, these pains can worsen around weeks 5–12 as steroid doses are tapered.
• Fatigue: Affecting 45% of patients, this isn’t just feeling tired—it’s a deep exhaustion that persists even with rest.
• Weakness: Noticed by 34% of patients, can also worsen as steroid doses decrease.
• Sleep disturbances: About 29% of patients struggled with poor sleep, which can exacerbate other symptoms.
• Mood changes and headaches: Around 19% and 17% of patients, respectively, reported these, impacting mental well-being.
• Other symptoms: Nausea, light-headedness, sweating, and difficulty concentrating were also noted, although less frequently.

These symptoms can ebb and flow, with some, like muscle pain and weakness, worsening as steroid doses are reduced. The study showed that patients with more severe Cushing syndrome at baseline (higher clinical severity scores) experienced worse GWS symptoms, highlighting the need for tailored post-surgical care.

Why Does GWS Happen, and How Long Does It Last?

GWS occurs because the body becomes dependent on high cortisol levels during active Cushing syndrome. When surgery rapidly corrects this excess, the HPA axis takes time to recover, and the brain and body struggle to adapt to lower cortisol levels. The Zhang et al. study found that GWS symptoms are most prominent in the first 12 weeks post-surgery.

While some symptoms, like sleep disturbances and headaches, may improve within this period, others, such as fatigue and muscle pain, can persist. The study suggests that the severity of pre-surgical Cushing syndrome influences the intensity and duration of GWS, with severe cases facing a tougher recovery. This underscores the importance of patience and close monitoring during this phase, as full HPA axis recovery can take months.

Why a High-Volume Center Matters

Choosing where to have your surgery for Cushing syndrome can make a significant difference in your outcome, including how GWS is managed. High-volume centers like the Carling Adrenal Center specialize in adrenal surgery, performing about 600 of these procedures annually. The Zhang et al. study emphasizes the value of expertise in achieving biochemical remission (nearly 100% for adrenal Cushing’s) and managing post-surgical complications like GWS.

High-volume centers offer:

• Surgical Expertise: Experienced surgeons, like Dr. Carling, are skilled in precise tumor removal, minimizing complications and ensuring remission and cure, which is critical to managing GWS effectively. He also performs a partial adrenalectomy, and that has proven to reduce the dose and duration of steroid replacement and thus reduces GWS.
• Multidisciplinary Care: Our expert team collaborates with endocrinologists and other doctors from around the country and internationally to tailor steroid tapering schedules and monitor GWS symptoms, adjusting treatment as needed.
• Patient Education: The study highlighted that patients often feel unprepared for the postoperative experience. High-volume centers provide comprehensive counseling to set realistic expectations about GWS and recovery.

At the Carling Adrenal Center, our team is dedicated to guiding patients through every step, from diagnosis to post-surgical recovery, ensuring that GWS is anticipated and managed proactively.

How to Navigate GWS with Your Care Team

Managing GWS requires a partnership between you and your medical team. Here are practical steps based on the study’s insights and our expertise at the Carling Adrenal Center:

• Monitor Symptoms Closely: Keep a symptom diary to track fatigue, muscle pain, or mood changes, and share this with your endocrinologist. The study used tools like a structured questionnaire to assess GWS, and similar systematic tracking can help your doctor adjust your steroid dose.
• Follow a Tailored Steroid Taper: Most patients in the study followed a standardized hydrocortisone taper (starting at 50 mg/day, reducing to 25 mg/day by week 6). Based on your cortisol levels, the day after adrenal surgery, you will be given an individualized dose and plan based on your specific results and needs. This is not a “one size fits all” situation, and our patients receive an individualized care plan. 
• Communicate Openly: If you feel unwell, don’t hesitate to contact your care team. The study noted that GWS is often underrecognized, so proactive communication is key.
• Seek Support: GWS can affect your quality of life, with the study showing a temporary worsening in physical health scores (SF-36). Counseling or support groups can help you cope with mood changes or fatigue.
• Choose Expert Care: Opt for a high-volume center with a track record of success in Cushing syndrome surgeries. The Carling Adrenal Center’s focused expertise ensures that your surgery and post-operative care, including GWS management, are optimized for the best outcomes.

Conclusion

Glucocorticoid Withdrawal Syndrome is a challenging but manageable part of recovery from Cushing syndrome surgery. By understanding its symptoms, expecting a potentially bumpy 12-week post-surgical period, and choosing a high-volume center like the Carling Adrenal Center, you can navigate GWS with confidence. The research by Zhang et al. underscores that GWS is common, influenced by the severity of your Cushing syndrome, and best managed with expert surgical and endocrinological care. If you’re facing cortisol-related issues, reach out to our team at the Carling Adrenal Center—we’re here to support you every step of the way.

Reference

• Zhang CD, Li D, Singh S, Suresh M, Thangamuthu K, Nathani R, Achenbach SJ, Atkinson EJ, Van Gompel JJ, Young WF, Bancos I. Glucocorticoid withdrawal syndrome following surgical remission of endogenous hypercortisolism: a longitudinal observational study. Eur J Endocrinol. 2023 Jul 10;188(7):592-602

Additional Resources: 

• Learn more about the Carling Adrenal Center
• Learn more about Dr. Tobias Carling
• Learn more about our sister surgeons at the Norman Parathyroid Center, and Clayman Thyroid Center.
• Learn more about the Hospital for Endocrine Surgery